tbuckley/cabot-search huggingface dataset:
Characterizing platinum sensitivity among Medicare FFS patients with limited versus extensive-stage small cell lung cancer receiving NCCN category 1 preferred regimens.
Authors: Paul Cockrum, Gabriela Dieguez, Rebecca A. Smith, Robert A. Ramirez
Journal: Journal of Clinical Oncology (2022)

e20601 Background: There is limited research evaluating real-world platinum sensitivity and treatment patterns among patients with limited vs. extensive stage small cell lung cancer (SCLC). Methods: We identified patients with SCLC in 2017 using ICD-10 diagnosis (Dx) and drug codes in the 2016-20 Medicare Parts A/B/D 100% Research Identifiable Files. Patients had 1+ lung cancer Dx and continuous enrollment in Parts A/B/D from the month prior to first Dx in 2017 (index) through 2020 or death. Patients with evidence of end-stage renal disease, prior lung or any metastatic cancer Dx within 12 months of index, lung resection/lobectomy, or use of a drug indicated only for non-SCLC or lung neuroendocrine cancer per NCCN guidelines were excluded. Use of systemic therapies cisplatin (ci), carboplatin (ca), etoposide intravenous (etIV), atezolizumab (at), durvalumab (du) and irinotecan (ir) were observed. Patients included in our study were treated with first-line NCCN Category 1 preferred regimens: ca/etIV, ca/etIV/at, ca/etIV/du, ca/ir, ci/etIV, ci/etIV/du, or ci/ir. First line of therapy (LoT1) was defined based on the first claim for a first-line regimen administered within 90 days following or up to 14 days before index. The end of LoT1 was defined as the earliest of death, 32 days after the last administration, or the start of a second line of therapy (LoT2). Patients initially treated with ca/etIV/at, ca/etIV/du, ca/ir, ci/etIV/du, or ci/ir regimens were flagged with extensive stage disease. Patients not receiving these regimens were classified as limited stage disease if they had 15+ days of radiation therapy over a 6-week period during or within 60 days of LoT1. Patients were deemed platinum sensitive (PS) if we did not observe a LoT2, hospice, or death within 6 months of LoT1. Uncategorizable patients were flagged Status Unknown (SU). All other patients were deemed platinum refractory (PR). Results: We identified 3,772 SCLC patients receiving NCCN Category 1 preferred regimens: 43% (1,607) had limited stage, and 57% (2,165) had extensive stage at index. Among patients with extensive stage, 71% (1,541) were PR compared with 34% (548) of patients with limited stage. On average, patients with extensive stage had fewer platinum cycles in LoT1 than those with limited stage. Conclusions: More platinum refractory patterns were observed among Medicare FFS patients with extensive stage SCLC than among patients with limited stage SCLC. Patients with extensive stage SCLC also underwent fewer platinum cycles in their first line of therapy.[Table: see text]
A remote evaluation of NAVIFY guidelines using simulation-based research methods.
Authors: Jack Halligan, Matthew Stewart Prime, Gianluca Fontana, Chaohui Guo, Anna Andoni, Saira Ghafur
Journal: Journal of Clinical Oncology (2022)

e13605 Background: This pilot study was designed to explore the use of remote simulation-based research methods to assess NAVIFY Guidelines, including data collection procedures. NAVIFY Guidelines is a software application that digitizes NCCN Guidelines and allows the user to navigate guidelines in a stepwise manner to support clinical decisions. The application has been designed to simplify access and improve adherence to guidelines in the management of oncology patients. Methods: A total of 10 board-certified oncologists were recruited to participate from large academic centers (5), community hospitals (3) and specialist oncology centers (2). Each oncologist reviewed clinical information for 10 synthetic breast cancer patient cases (i.e., 100 case reviews). The cases were developed by a medical oncologist, a surgical oncologist, a radiologist and a histopathologist. Participants were tasked to select the most appropriate clinical decision as per guidelines in two conditions: 1) using a PDF of the NCCN Guidelines (control), and 2) using NAVIFY Guidelines (experimental). Outcome measures were compared across conditions. Sessions were conducted via Google Meet, with participants using the share screen feature to allow the session to be recorded. The cognitive burden of each method was measured via a psychometric test conducted before and after each method (the Stroop Colour and Word Test). After each session, a post-simulation survey gathered feedback on 1) study methods, 2) use of synthetic patient cases, 3) workload effort required (via the NASA Task Load Index), and 4) usability of NAVIFY Guidelines (via the System Usability Scale). A short interview was conducted after each session to gather feedback on the benefits and challenges of using NAVIFY Guidelines and to discuss the participant’s experience of the simulation session. Results: All data collection procedures were successful including 1) assessment of time taken to reach a clinical decision, 2) psychometric testing, 3) survey data, and 4) user feedback. All participants felt the synthetic patient cases were either ‘very similar’ (7 of 10) or ‘somewhat similar’ (3 of 10) to cases seen in routine clinical practice, and the majority felt the task completed during the sessions was ‘very similar’ (3 of 10) or ‘somewhat similar’ (4 of 10). Conclusions: Remote evaluations can be conducted quickly helping to keep pace with product development cycles. The method is easily repeated therefore supporting evaluation of product development over time. In addition, managing simulations remotely enables the possibility of simultaneous evaluations across multiple geographies, and the use of synthetic patient data eliminates data protection concerns. This study suggests that simulation-based research can be used to assess digital health solutions remotely in a timely fashion.
Health-related quality of life (HRQoL) in patients with relapsed/refractory multiple myeloma (RRMM) receiving real-life current standard of care (SOC) in the LocoMMotion study.
Authors: Michel Delforge, Philippe Moreau, Hermann Einsele, Valerio De Stefano, Joanne Lindsey-Hill, Laure Vincent, Silvia Mangiacavalli, Aurore Perrot, Enrique Ocio, Silene ten Seldam, Ester in ’t Groen-Damen, Maria Semerjian, Vadim Strulev, Jordan Mark Schecter, Tito Roccia, Katharine S. Gries, Tonia Nesheiwat, Robert Wapenaar, Maria-Victoria Mateos, Katja Weisel
Journal: Journal of Clinical Oncology (2022)

8030 Background: Evaluation of patient (pt)-reported outcomes provides insight into how real-life SOC treatments (tx) affect HRQoL for pts with RRMM. LocoMMotion (NCT04035226) is the first prospective, multinational study of real-life SOC in triple-class exposed pts with RRMM. Here, we present measures of symptoms, functioning, and overall HRQoL. Methods: LocoMMotion is a prospective, noninterventional study across 76 sites (63 European; 13 US). Pts had received ≥3 prior lines of therapy (LOT) or were refractory to PI and IMiD; received PI, IMiD, and anti-CD38 mAb; and had disease progression during/after last LOT. Real-life SOC tx were defined as those used in local clinical practice. The questionnaires were EORTC QLQ-C30, 4 single items from EORTC QLQ-MY20, and EQ 5D-5L. HRQoL was assessed at baseline (BL), day 1 of each tx cycle, end of tx visit, and during the follow-up period (every 4 weeks). Improvement compared to BL health status was evaluated using established thresholds. Within-group change was assessed using mixed models for repeated measures. Results: Questionnaire completion for pts in the LocoMMotion study (N=248; 54.4% male; median age 68 yrs; median 4.0 [range, 1–20] cycles of SOC) was 75.6% during SOC tx. Most pts did not achieve meaningful improvement in PRO scores, defined by a literature-based minimally important difference of 10 points in mean score. This was most pronounced in pain symptoms (62% of pts had no meaningful improvement during the first 3 months of tx; 55% had no improvement during full tx duration). For the overall population, the least square (LS) mean changes from BL during SOC tx and subsequent LOT are described (Table). Pts who achieved very good partial response and better during SOC tx had greater improvement in PRO scores, including in LS mean change for pain score (-14.9 [95% confidence interval (CI): -22.9, -7.0]). Conclusions: In this first prospective study of real-life current SOC in triple-class exposed pts, limited gains in HRQoL were reported, most notably in pain symptoms. There is an urgent need for effective therapies that can help pts achieve deep responses and delay disease progression, as these are associated with improved HRQoL. Clinical trial information: NCT04035226. [Table: see text]
Platinum-doublet chemotherapy for advanced gastroenteropancreatic neuroendocrine carcinoma: A systematic review and meta-analysis.
Authors: Akihiro Ohmoto, Yu Fujiwara, Nobuyuki Horita, Kenji Nakano, Shunji Takahashi
Journal: Journal of Clinical Oncology (2022)

e16217 Background: Neuroendocrine carcinoma (NEC) is a poorly differentiated pathological neuroendocrine neoplasm exhibiting aggressive clinical behaviors; the most common extrapulmonary site is the gastroenteropancreatic (GEP) system. Treatment strategies for GEP-NEC are primarily based on those employed for small cell lung cancer, and platinum-doublet chemotherapy, such as platinum plus etoposide (EP) or platinum plus irinotecan (IP), has been widely used as initial systemic therapy for patients with advanced/metastatic disease; however, clinical data for GEP-NEC are chiefly derived from small-scale retrospective studies, and the reported efficacy is heterogenous among studies. Methods: We conducted a systematic database search using PubMed/MEDLINE and EMBASE. Eligible studies included randomized trials, single-arm trials, prospective observational studies, and retrospective studies documenting the clinical efficacy of platinum-doublet chemotherapy (EP and IP) for advanced GEP-NEC. The pooled overall response rate (ORR), median progression-free survival (PFS), and median overall survival (OS) were calculated and weighted using generic inverse variance in a random-effects meta-analysis model. Results: Based on initial screening and eligibility assessment, 19 studies with a combined total of 1,157 patients were identified through a systematic review. Studies included 3 comparative studies between EP and IP with 1 randomized phase II trial and 2 retrospective studies. The pooled ORR in all patients who received the platinum-doublet regimen was 49.1% (95% confidence interval [CI], 41.8–56.5), and subgroup analysis for EP and IP groups showed ORRs of 44.4% (95% CI, 35.9–53.0) and 59.4% (95% CI, 48.0–70.8), respectively. According to the three studies directly comparing EP to IP, the odds ratio of ORR using EP as reference was 1.95 (95% CI, 0.86–4.39, P = 0.11). The pooled median OS in all patients who received the platinum-doublet regimen was 12.9 (95% CI, 10.9–15.3) months, where EP and IP subgroups had median OS of 12.9 (95% CI, 10.8–15.4) and 12.9 (95% CI, 6.0–27.8) months, respectively. The pooled median PFS was 5.4 (95% CI, 4.5–6.4) months in all patients with platinum-regimen, 5.4 (95% CI, 4.5–6.5) months in the EP subgroup, and 4.0 (95% CI, 1.4–11.7) months in IP subgroup, respectively. Conclusions: This study was the first systematic review and meta-analysis assessing patients with GEP-NEC; it has revealed considerable ORR following platinum-doublet chemotherapy. EP and IP regimens can be reasonably employed in patients with advanced GEP-NEC. These results can serve as reference information for clinicians in deciding a suitable chemotherapy regimen. Larger randomized trials and individual patient data meta-analyses are warranted to obtain robust clinical evidence.
First-line (1L) treatment patterns in advanced non-small cell lung cancer (NSCLC) patients (pts) who are elderly or have compromised performance status (PS).
Authors: Julia Judd, Elizabeth A. Handorf, Brinda Gupta, Martin Joseph Edelman
Journal: Journal of Clinical Oncology (2022)

e18783 Background: Previous studies demonstrated that pts &gt; 80 years (80+), or compromised PS (ECOG PS &gt; 2, PS 2+) are frequently not treated for advanced NSCLC, despite studies demonstrating survival benefit with active therapy. We hypothesized that new therapies (e.g., immunotherapy) have changed practice in these populations. Here, we present new subgroup analysis in pts 80+ or PS2+. Methods: We conducted a retrospective, observational cohort study using the nationwide Flatiron Health electronic health record (EHR)-derived de-identified database to describe 1L treatment patterns from 2011 to 2020 in pts with advanced NSCLC. Pts 80+ could only be included from 2015 as the database suppressed birth years prior to 1935 due to privacy protection. Pts were excluded if there was a &gt; 90-day post-diagnosis gap in EHR data. Treatment groups included PD-1/PD-L1 inhibitor single agent, chemoimmunotherapy, platinum-based doublet +/- VEGF inhibitors (VEGFi), single agent chemotherapy and tyrosine kinase inhibitors (TKIs). Descriptive statistics were used to analyze treatment patterns by year, and the relationship between 1L treatments and variables of interest were tested using Cochran-Armitage trend tests. Results: Of 58,145 pts with advanced NSCLC in the database, 6,528 were 80+ (2015+) and 8,611 had PS2+ at diagnosis (2011+). While the proportion of pts who did not receive any documented treatment has decreased for those 80+ (p &lt; 0.0001), the proportion remains the same in pts with PS2+ (p = 0.78; Table). There was rapid uptake of PD-1/PD-L1 inhibitors as well as chemoimmunotherapy upon FDA approvals in 2016 and 2018, respectively. This correlated with a rapid decrease in platinum-doublet chemotherapy +/- VEGFi and single agent chemotherapy use. Single agent immunotherapy was favored in pts 80+ (Table). TKIs accounted for 9-11% of treatment employed in pts 80+ and 6-8% in pts with PS2+, without notable change across the study period. Conclusions: Real world data from 2011 to 2020 demonstrates rapid incorporation of immunotherapy into 1L treatment for NSCLC pts who are 80+ or PS2+. A substantial proportion of pts in these subgroups (32.8% and 35.1%, respectively) still do not receive treatment. [Table: see text]
Practice consolidation among U.S. medical oncologists over time.
Authors: Michael Milligan, Parsa Erfani, E. John Orav, Gabriel A. Brooks, Miranda Lam
Journal: Journal of Clinical Oncology (2022)

e13627 Background: Physician practices across the U.S. are increasingly merging with hospitals and other practices. The extent of such “practice consolidation” varies by specialty and across geography but has not been well characterized within medical oncology. Methods: Utilizing Medicare data, we identified all medical oncologists (MO) who billed for Medicare services each year between 2015 and January 2022. We associated each physician to one or more unique practices via organizational Taxpayer Identification Numbers (TIN), and classified practices by the number of medical oncologists—including solo (1 MO), small (2-10 MOs), medium (11-24 MOs), and large (25+ MOs) practices. We defined the extent of regional healthcare markets according to Hospital Referral Regions (HRRs), and calculated levels of practice consolidation using the Herfindahl-Hirschman Index (HHI). The HHI is a commonly used measure of consolidation, calculated by summing the square of each practice’s market share. HHI values range from 0 to 1 with higher numbers indicating greater consolidation and less competition among practices. Finally, we generated a multivariable linear regression model to determine which regional market factors were associated with changes in levels of medical oncology practice consolidation over time. Results: Between 2015 and 2022, the number of practices with MOs in the U.S. declined 18.0% from 2,774 to 2,276, while the number of practicing MOs increased 14.5% from 11,727 to 13,433. The median medical oncology practice HHI increased from 0.3204 to 0.3480. Over time the proportion of solo practices fell (48.4% in 2015, 43.9% in 2022) while the proportion of medium and large practices increased (medium: 5.7% to 8.4%; large: 2.7% to 4.5%). By 2022, large practices had grown to employ a significantly larger proportion of all medical oncologists (33.6% to 43.7%, p &lt; 0.001). Between 2015 and 2022, the proportion of practices solely comprised of MOs (as opposed to multispecialty practices) decreased from 40.0% to 28.2%. On multivariable analysis, HRRs with higher levels of hospital consolidation (p &lt; 0.001), greater numbers of hospital beds per 1,000 persons (p = 0.02), and a lesser degree of baseline medical oncology practice consolidation in 2015 (p &lt; 0.001) experienced more consolidation during the study period. Conclusions: Medical oncologists across the U.S. are increasingly working in larger practices. By 2022, more than 40% of all practicing MOs were employed at the largest 5% of practices. Consolidation of medical oncology practices occurred more readily in regions with higher levels of hospital consolidation and a greater supply of hospital beds, suggesting that integration into hospital systems may be a leading source of consolidation. Further study is required to determine the impact of practice consolidation on the cost, quality, and accessibility of cancer care.
Outcomes in non-small cell lung cancer (NSCLC) patients treated with second-line therapy after progression or recurrence after initial first line immune checkpoint-based therapy.
Authors: Ibrahim Muhsen, Charisma Mylavarapu, Humaira Sarfraz, Sunil Mathur, Eric Bernicker
Journal: Journal of Clinical Oncology (2022)

e21027 Background: The use of immune checkpoint inhibitors (ICI) based therapies, including in combination with platinum-based or as monotherapy, is currently the standard of care in stage IV NSCLC patients as a first line therapy. However, there is limited data on the options and outcomes of NSCLC patients if they progress after first-line therapy. This study aims to investigate the clinical outcomes to second lines of treatment for these patients. Methods: This is a retrospective study conducted at Houston Methodist Hospital involving adult patients (&gt; 18 years old) with metastatic stage IV NSCLC who received ICI based therapy (combination or monotherapy) for the treatment of NSCLC and subsequently progressed or recurred and received a second line of therapy between 11/1/2016 and 12/31/2019. We excluded patients with targetable driver mutations (except KRAS) and patients with a concurrent cancer diagnosis. We collected information on the second line of therapy received and evaluated outcomes including progression-free survival (PFS), overall survival (OS) and overall response rate (ORR). PFS was defined from time of second-line therapy initiation to time of documented recurrence/progression. ORR was defined as patients who achieve partial response (PR) or complete response (CR). The Kaplan Meier method was used for survival analysis. Results: Among patients who received ICI-based first line therapy, 32 patients were identified to meet the inclusion criteria. Twenty-seven (84%) patients had adenocarcinoma and 17 patients had negative PD-L1 stain. Twenty-seven (84%) patients received a combination of carboplatin, pembrolizumab, and pemetrexed, whereas five (16%) patients received ICI monotherapy (3 pembrolizumab, 1 nivolumab and 1 durvalumab). Thirteen patients had an initial response to first-line therapy (11 PR, 2 CR). After progression/recurrence, various therapies were administered as second-line with the most common being the use of ICI + chemotherapy combination (6 pts, 19%) or ramucirumab + taxotere combination (6 pts, 19%). The remaining patients received other types of chemotherapy, targeted therapy, ICI, or were enrolled in a clinical trial. Nine patients (28%) had a response after 2 nd line therapy [4 CR and 5 PR], 16 (50%) had progressive disease, and 5 (16%) had mixed response/stable disease. The cohort median PFS after 2 nd line of therapy was 16.9 weeks (95% CI: 14.4-19.3). Conclusions: These findings reflect the variability in practices in stage IV NSCLC patients who progress after receiving ICI-based first line therapy. Outcomes of patients who progress after their first line remain suboptimal with short-lived responses. Further studies are needed to investigate the efficacy and safety of different second line treatment options.
Metagenomic analysis of the fecal microbiome in patients with colorectal cancer compared to healthy controls as a function of age.
Authors: Jordan Kharofa, Senu Apewokin, Theresa Alenghat, Nicholas Ollberding
Journal: Journal of Clinical Oncology (2022)

3532 Background: Colorectal cancer (CRC) incidence is increasing in young patients ( &lt; 50 years old) without a clear etiology. Emerging data has implicated the fecal microbiome in CRC carcinogenesis. However, its impact on young onset CRC (YO-CRC) is poorly defined. Colibactin producing E. Coli and fadA producing Fusobacterium nucleatum can drive CRC carcinogenesis, however their effects across the age spectrum are unknown. Methods: We performed a meta-analysis of fecal metagenomics sequencing from n = 692 patients with CRC and n = 602 healthy controls from eleven studies to evaluate species and known microbial derived factors (colibactin and FadA) associated with CRC as a function of age. Generalized linear mixed effects regression was used to model the predicted prevalence of gene families and taxa as a non-linear function of age. Two-stage individual patient data meta-analysis (IPDMA) with adjustment for gender, CRC status, and body mass index was also used to estimate summary odds ratios for colibactin, F. nucleatum, and E. Coli. Interaction ORs were obtained to assess the difference in the effect of each gene or taxa on CRC case status in YO-CRC. Shannon Diversity index and metabolic pathway differences in the fecal metagenome for YO-CRC patients were assessed using phyloseq and MetaCyc respectively using an IPDMA approach. Results: Summary odds ratios (OR) for CRC were increased relative to controls with the presence of colibactin (OR 1.92 95%CI 1.08-3.38), fadA (OR 4.57 95%CI 1.63-12.85), and F. nucleatum (OR 6.93 95%CI 3.01-15.96) in models of all patients adjusted for age, gender, and body mass index. The OR for CRC for the presence of E.coli was 2.02 (0.92-4.45). An increase in the prevalence of F. nucleatum (OR = 1.40 [1.18; 1.65] and Escherichia coli (OR = 1.14 [1.02; 1.28]) per 10-year increase in age was observed in models including samples from both CRC and healthy controls. No difference was observed for Shannon Diversity (OR 1.36 95%CI 0.68-2.72) or MetaCyc pathways in YO-CRC patients. Species relative abundance was differentially enriched in YO-CRC relative to old CRC patients and controls for five species- Intestinimonas butyriciproducens, Holdemania filiformis, Firimicutues bacterium CAG 83, Bilophilia wadsworthia, and Alistipes putredinis. Conclusions: Strong associations with CRC status were observed for colibactin, fadA, and F. nucleatum with increased F. nucleatum in older patients. Several species were enriched in YO-CRC patients including B. wadsworthia which can produce carcinogenic sulfur metabolites and is increased with adherence to a sulfur microbial diet-low in vegetables and legumes. A sulfur microbial diet has also been associated with higher incidence of YO-CRC in population studies (Nguyen Gastroenterology 2021). Additional study is warranted to understand causal mechanisms of enriched species observed in YO-CRC patients.